1. Field of the Invention
The present invention provides methods for treating parasitic infections in animals using thiopeptides. In particular, this invention relates to the treatment of parasitic infections caused by members of the phylum Apicomplexa (e.g., Cryptospordium, Plasmodium, Toxoplasma) by administering thiopeptides in a pharmaceutically acceptable carrier.
2. Background Art
Thiopeptides are sulfur-rich peptide antibiotics containing multiple thiazole rings which are naturally produced by streptomycetes (37). These antibiotics, of which thiostrepton is an example, inhibit translation and ribosomal GTPase activity by binding to a limited and conserved region in the large subunit (LSU) rRNA found in eubacteria and organelles and not the corresponding region in eucarya (12-14).
Plasmodium, the agent responsible for malaria, is an obligate intracellular parasite. More than ten years ago an urgent need for drugs against malaria was identified (33). The antibiotics currently in use, including the tetracyclines and clindamycin, for the treatment and prophylaxis of malaria have little action on pre-erythrocytic stages and a slow action on blood stages, but are used for treatment of drug resistant strains because of their safety rather than their efficacy (34,35). Furthermore, the rapid spread of resistance to chloroquine has heightened the need for ready availability of relatively low cost prophylactic and therapeutic anti-malarial drugs. These include compounds that reverse resistance to chloroquine, compounds that act rapidly to treat falciparum malaria and others that can be administered by methods other than injection (to avoid the use of contaminated needles).
Human clinical cryptosporidiosis infection varies with host immune competence from mild, self-limiting diarrhea to life-threatening enteritis complicated by extraintestinal disease. There is no reliable therapy for cryptosporidiosis. The problems of developing in vitro and in vivo methods of screening drugs, such as limited availability and poor reproducibility, have contributed to this lack of effective treatment. However, the major hindrance has been a lack of understanding of the parasite, its virulence and its interactions with the host's immune system (42).
The present invention overcomes previous shortcomings in developing effective treatments of these types of parasitic infections by providing a method for treating such infections in subjects caused by parasites having a plastid-like organelle by administering thiopeptides to the subject.